The epidemiology of lung cancer, the leading cause of cancer mortality in men and women, has changed considerably over the past several decades. We have observed and reported that both the content of manufactured tobacco and the pathology of the disease have undergone marked changes since 1950. In particular, over the past several decades there has been a disproportionate increase in adenocarcinoma over squamous cell carcinoma of the lung, while during the same period the tar and nicotine content of cigarettes fell by more than 60%. It is our working hypothesis that dramatic changes in the histologic type and anatomic location of lung tumors observed during the past several decades are directly related to the marketplace shift in the types of cigarettes smoked by different segments of the population. For this Project we propose the following aims: (1) to study the risk of lung cancer by histology type in relation to low- and higher-yield cigarettes; (2) to determine whether women are at a greater risk for lung cancer than men for a given level of smoking, and whether other gender-related factors such as estrogen replacement therapy are associated with increased lung cancer risk; (3) to determine whether blacks are at a greater risk for lung cancer than whites for a given level of cigarette smoking; and (4) using our historic data base and research infrastructure, to continue to respond rapidly to emerging and unresolved issues related to lung cancer, including (a) risks associated with exposure to diesel engine exhaust, (b) a possible protective effect of nonsteroidal anti-inflammatory drugs, and (c) determination of the reliability of assessment of exposure to environmental tobacco smoke in nonsmoking cases and controls.